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Purity: ≥98%
Fosaprepitant dimeglumine (also known as L-758298 dimeglumine; MK0517 dimeglumine) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Fosaprepitant is injected intravenously as an antiemetic medication. Merck & Co. created fosaprepitant, which was authorized as an Aprepitant prodrug. It helps to prevent both acute and delayed nausea and vomiting brought on by chemotherapy. Aprepitant, the active moiety, is a substrate, inducer, and inhibitor of CYP3A4, while fosaprepitant is a weak inhibitor of CYP3A4.
Targets |
Neurokinin-1 receptor
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ln Vitro |
Fosaprepitant (MK-0517, L-758,298) is a phosphoryl prodrug for aprepitant. A corticosteroid and a 5-HT 3 receptor antagonist are approved as combination therapies with the selective substance P (NK-1 receptor) antagonist aprepitant to prevent acute and delayed chemotherapy-induced nausea and vomiting. [1]
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ln Vivo |
Fosaprepitant is intravenously administered and within 30 minutes, transforms into an aprepitant due to the action of ubiquitous phosphatases. Fosaprepitant has a well-tolerated maximum dosage of 150 mg (1 mg/ml), and its AUC for Fosaprepitant 115 mg and Aprecipitant 125 mg are bioequivalent. On day 1 of a 3-day oral aprepitant regimen, fosaprepitant 115 mg has been submitted for FDA approval as an alternative. On days 2 and 3, oral aprepitant is administered. [1]
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Animal Protocol |
Sprague-Dawley rats were injected with morphine (10 mg/kg twice daily) and/or fosaprepitant (30 mg/kg once daily) for 7 days. Pain threshold was assessed by the hot plate test. Expression of SP and calcitonin gene-related peptide (CGRP) in the spinal cords of these rats was evaluated by immunohistochemistry.[2]
Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion of fosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant 115 mg was generally well tolerated at a final drug concentration of 1 mg/ml, and fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg. Fosaprepitant in the dose of 115 mg has been approved by the US FDA, the EU and the Australian authorities on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the utility of fosaprepitant in the prevention of CINV and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant[2]. |
References |
[1]. Expert Opin Investig Drugs. 2007 Dec;16(12):1977-85. [2]. Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats. Indian J Pharmacol. 2016 Jul-Aug; 48(4): 394-398.[3]. Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther . 2008 Nov;8(11):1733-42. |
Additional Infomation |
Fosaprepitant dimeglumine is an organoammonium salt obtained by reaction of fosaprepitant with two equivalents of 1-deoxy-1-(methylamino)-D-glucitol. A substance P/neurokinin 1 (NK1) receptor antagonist. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting It has a role as a prodrug, an antiemetic and a neurokinin-1 receptor antagonist. It contains a fosaprepitant(2-).
ChEBI
Fosaprepitant Dimeglumine is the dimeglumine salt form of fosaprepitant, the water-soluble, N-phosphorylated prodrug of aprepitant, with antiemetic activity. Upon intravenous administration and rapid conversion to aprepitant, this agent binds selectively to the human substance P/neurokinin 1 (NK1) receptors in the central nervous system (CNS). This inhibits receptor binding of the endogenous substance P and prevents substance P-induced emesis. Prevention of nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults and paediatric patients aged 6 months and older. Ivemend 150 mg is given as part of a combination therapy. Purpose: Fosaprepitant dimeglumine for injection is the water-soluble phosphorylated prodrug of the neurokinin-1 receptor antagonist aprepitant. Both agents are approved (in combination with a 5-HT3 antagonist and a corticosteroid) for prevention of chemotherapy-induced nausea and vomiting. Because fosaprepitant is likely to be combined and stored in the same intravenous (IV) bag with 5-HT3 antagonists and corticosteroids, the in vitro compatibility of fosaprepitant with these agents and other IV diluents was assessed.[3] Methods: Fosaprepitant (1 mg/mL in 0.9 % sodium chloride injection solution) was combined in binary or tertiary fashion with therapeutic-dose preparations of a 5-HT3 antagonist (ondansetron, granisetron, palonosetron, or tropisetron) and/or a corticosteroid (dexamethasone sodium phosphate or methylprednisolone sodium succinate). For diluent compatibility assessment, fosaprepitant was also prepared 1 mg/mL in 0.9 % sodium chloride injection solution, water for injection, or 5 % dextrose injection solution. After 24-h storage under ambient conditions, samples were assayed for degradation.[3] Results: Fosaprepitant demonstrated compatibility when combined in the same IV infusion bag with common 5-HT3 antagonists and corticosteroids for storage and IV coadministration, with the exception of palonosetron (incompatible under all experimental conditions) and tropisetron (incompatible unless combined with a corticosteroid). No incompatibility was observed between fosaprepitant and any of the 3 diluents tested.[3] Conclusions: Use of fosaprepitant in combination with other antiemetics may provide a flexible option for administration of antiemetics to patients receiving moderately or highly emetogenic chemotherapy.[3] |
Molecular Formula |
C37H56F7N6O16P
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Molecular Weight |
1004.8337
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Exact Mass |
1004.34
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Elemental Analysis |
C, 44.23; H, 5.62; F, 13.23; N, 8.36; O, 25.48; P, 3.08
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CAS # |
265121-04-8
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Related CAS # |
Fosaprepitant; 172673-20-0; Fosaprepitant-d4 dimeglumine
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PubChem CID |
135564864
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Appearance |
White solid powder
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tPSA |
366.08
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SMILES |
C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](N(CCO2)CC3=NN(C(=O)N3)P(=O)(O)O)C4=CC=C(C=C4)F.CNC[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.CNC[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O
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InChi Key |
VRQHBYGYXDWZDL-OOZCZQCLSA-N
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InChi Code |
InChI=1S/C23H22F7N4O6P.2C7H17NO5/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)40-20-19(13-2-4-17(24)5-3-13)33(6-7-39-20)11-18-31-21(35)34(32-18)41(36,37)38;2*1-8-2-4(10)6(12)7(13)5(11)3-9/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38);2*4-13H,2-3H2,1H3/t12-,19+,20-;2*4-,5+,6+,7+/m100/s1
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Chemical Name |
[3-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-5-oxo-4H-1,2,4-triazol-1-yl]phosphonic acid;(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol
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Synonyms |
MK0517; MK 0517; MK-0517; Fosaprepitant dimeglumine; Fosaprepitant dimeglumine salt; Ivemend; Fosaprepitant meglumine; MK-0517; Fosaprepitant (dimeglumine); UNII-D35FM8T64X; Emend; Inemend
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product is not stable in solution, please use freshly prepared working solution for optimal results. (2). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
H2O: ~50 mg/mL (~49.8 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (99.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
 (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 0.9952 mL | 4.9760 mL | 9.9519 mL | |
5 mM | 0.1990 mL | 0.9952 mL | 1.9904 mL | |
10 mM | 0.0995 mL | 0.4976 mL | 0.9952 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT05755659 | Recruiting | Drug: Fosaprepitant Dimeglumine for Injection |
Neoplasms | Xijing Hospital | July 15, 2022 | Not Applicable |
NCT01504711 | Completed | Drug: fosaprepitant dimeglumine | Gastrointestinal Cancer Nausea Post Chemotherapy |
Philip Philip | June 2012 | Not Applicable |
NCT04054193 | Completed | Drug: Fosaprepitant Dimeglumine Drug: Dexamethasone |
Chemotherapy-induced Nausea and Vomiting |
Merck Sharp & Dohme LLC | September 9, 2019 | Phase 4 |
NCT01074697 | Completed | Drug: Fosaprepitant dimeglumine Drug: Placebo |
Nausea Vomiting |
Odense University Hospital | April 2010 | Phase 3 |
NCT01594749 | Completed | Drug: Dexamethasone Drug: Ondansetron |
Chemotherapy-Induced Nausea and Vomiting (CINV) |
Merck Sharp & Dohme LLC | September 24, 2012 | Phase 3 |
Quantitative image analysis of the expression of substance P and calcitonin gene-related peptide (CGRP) shows that morphine + fosaprepitant treatment led to higher substance P expression compared to all other groups including the morphine treated group. ≠≠≠P < 0.001. Fosa represents fosaprepitant. Indian J Pharmacol . 2016 Jul-Aug;48(4):394-398. td> |